Presentations highlight Celgene’s ongoing
innovative research, including the use of CAR T cell therapies to
treat multiple myeloma and lymphoma, and therapies for the
treatment of multiple blood disorders, including multiple myeloma,
lymphoma, leukemia, myelodysplastic syndromes and
beta-thalassemia
Celgene Corporation (NASDAQ:CELG) today announced that data from
a broad range of early and late stage studies evaluating Celgene
investigational agents and investigational uses of marketed
products will be presented at the 23rd European Hematology
Association (EHA) annual meeting in Stockholm, Sweden,
from June 14-17, 2018.
"We are proud to be sharing new and updated data around our
innovative hematological therapies at EHA 2018, which further our
understanding of blood cancers and other blood-related diseases and
allow us to continue to have a major impact on the lives of
patients," said Nadim Ahmed, President, Hematology &
Oncology Franchise. "The data presented at EHA underscore the
important role of immunomodulatory drugs at various stages of
multiple myeloma, as well as illustrate our ongoing work in
developing innovative treatment options, such as our erythroid
maturation agent and CAR T cell therapies, for patients with life
threatening blood disorders and cancers."
At EHA this year, data will be presented on Revlimid in both
Newly Diagnosed Multiple Myeloma and as maintenance treatment, and
Pomalyst combination regimens following Revlimid use, including new
data from the Phase III OPTIMISMM trial in the relapsed/refractory
setting. Results from the Phase III RELEVANCE study of lenalidomide
plus rituximab (R2) versus rituximab plus chemotherapy, followed by
rituximab, in previously untreated follicular lymphoma patients
will be featured during the meeting’s Presidential Symposium. Data
will also be presented on Celgene’s CAR T cell therapies, including
updated findings on bb2121 in multiple myeloma and pivotal clinical
data on JCAR017 in lymphoma. Additionally, 2-year safety and
efficacy data on luspatercept, an investigational compound, in
beta-thalassemia will be presented.
Selected abstracts include:
CAR T
Abstract #S138; Oral; Friday, June 15, 12.30 – 12.45,
Room A8. bb2121 anti-BCMA CAR T cell therapy in patients with
relapsed/refractory multiple myeloma: updated results from a
multicenter Phase I study. (Raje)
Abstract #S800; Oral; Saturday, June 16, 11:45 –
12:00, Room A1. Updated safety and long term clinical outcomes in
TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel
(JCAR017) in r/r aggressive NHL (Abramson)
Newly-diagnosed Multiple
Myeloma
Abstract #PS1429; Poster Presentation; Saturday, June
16, 17:30 – 19:00. Cost comparison of treatment strategies
following initiation with Rd versus VMP plus daratumumab in newly
diagnosed patients ineligible for ASCT. (Jackson)
Abstract #PF570; Poster Presentation; Friday, June 15,
17:30 – 19:00. Development of a predictive model of multiple
myeloma (MM) patient outcomes based on treatment (tx) sequencing
using data from The Connect® MM Patient Registry. (Jagannath)
Relapsed/Refractory Multiple
Myeloma
Abstract #S847; Oral; Saturday, June 16, 16:00 – 16:15,
Room A1. OPTIMISMM: Phase III trial of pomalidomide, bortezomib,
and low‐dose dexamethasone vs bortezomib and low-dose dexamethasone
in lenalidomide-exposed patients with relapsed or refractory
multiple myeloma. (Richardson)
Abstract #PF567; Poster Presentation; Friday, June 15,
17:30 – 19:00. Safety and efficacy of pomalidomide plus low-dose
dexamethasone immediately following lenalidomide-based treatment
failure in patients with relapsed and/or refractory multiple
myeloma. (Siegel)
Abstract #PS1292; Poster Presentation; Saturday, June
16, 17:30 – 19:00. Pomalidomide plus low-dose dexamethasone
plus daratumumab in patients with relapsed and/or refractory
multiple myeloma after lenalidomide-based treatment failure.
(Siegel)
Abstract #PF576; Poster Presentation; Friday, June 15,
17:30 – 19:00. Safety outcomes in patients with relapsed/refractory
multiple myeloma (RRMM) treated with lenalidomide for ≤ 24 months
vs > 24 months in a European post-approval safety study (EU
Pass). (Semenzato)
Maintenance in Multiple Myeloma
Abstract #PF562; Poster Presentation; Friday, June 15,
17:30 – 19:00. Maintenance after lenalidomide, bortezomib, and
dexamethasone induction and transplant in patients with newly
diagnosed multiple myeloma and high-risk cytogenetics: an enhanced
medical record analysis. (Fonseca)
Acute Myeloid Leukemia
Abstract #PS980; Poster Presentation; Saturday, June
16, 17:30 – 19:00. Continuing enasidenib treatment for
patients with mutant-IDH2 relapsed/refractory acute myeloid
leukemia (r/r AML) with stable disease may result in improved
responses and survival over time. (Stein)
Abstract #S1562; Oral; Sunday, June 17, 08:30 – 08:45,
Victoria Hall. Mutant IDH (MIDH) inhibitors, ivosidenib or
enasidenib, with azacitidine (AZA) in patients with acute myeloid
leukemia (AML). (DiNardo)
Lymphoma
Abstract #S154; Oral; Friday, June 15, 17:00 – 17:15, Room
A1. RELEVANCE: Phase III efficacy and safety study of lenalidomide
plus rituximab (R2) versus rituximab plus chemotherapy, followed by
rituximab, in previously untreated follicular lymphoma.
(Morschhauser)
Beta-Thalassemia
Abstract #S844; Oral; Saturday, June 16, 12:00 –
12:15, Room K2. Improvements in hemoglobin, quality of life, and
six-minute-walk distance in adults with β-thalassemia treated with
luspatercept: long-term Phase II study. (Piga)
The safety and efficacy of the agents and/or uses under
investigation have not been established. There is no guarantee that
the agents will receive health authority approval or become
commercially available in any country for the uses being
investigated.
A complete listing of abstracts can be found on the EHA
Learning Center Web site at
https://learningcenter.ehaweb.org/eha.
About Celgene’s Immunomodulatory Drugs
Immunomodulatory Drugs (IMiDs®) are Celgene’s proprietary small
molecule, orally available compounds for the treatment of some
blood cancers. IMiDs® are the foundation of multiple myeloma
treatment, driven by the proven survival benefits across lines of
therapy. Their mechanism of action is well defined and offers the
combination of striking tumor cells, stimulating the immune system,
and synergizing with other classes of treatment. With REVLIMID®
(lenalidomide) and POMALYST®/IMNOVID® (pomalidomide), Celgene has a
portfolio of innovative medicines that have helped transform the
treatment of multiple myeloma, providing patients longer disease
control at every stage of the disease from newly diagnosed to
relapse refractory multiple myeloma.
About REVLIMID
REVLIMID in combination with dexamethasone (dex) is indicated
for the treatment of patients with multiple myeloma (MM)
REVLIMID is indicated as maintenance therapy in patients with MM
following autologous hematopoietic stem cell transplantation
(auto-HSCT)
REVLIMID is indicated for the treatment of patients with
transfusion-dependent anemia due to low-or intermediate-1-risk
myelodysplastic syndromes (MDS) associated with a deletion 5q
cytogenetic abnormality with or without additional cytogenetic
abnormalities
REVLIMID is indicated for the treatment of patients with mantle
cell lymphoma (MCL) whose disease has relapsed or progressed after
two prior therapies, one of which included bortezomib
REVLIMID is not indicated and is not recommended for the
treatment of patients with chronic lymphocytic leukemia (CLL)
outside of controlled clinical trials
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC
TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal
Toxicity
Do not use REVLIMID during pregnancy. Lenalidomide, a
thalidomide analogue, caused limb abnormalities in a developmental
monkey study. Thalidomide is a known human teratogen that causes
severe life-threatening human birth defects. If lenalidomide is
used during pregnancy, it may cause birth defects or embryo-fetal
death. In females of reproductive potential, obtain 2 negative
pregnancy tests before starting REVLIMID treatment. Females of
reproductive potential must use 2 forms of contraception or
continuously abstain from heterosexual sex during and for 4 weeks
after REVLIMID treatment. To avoid embryo-fetal exposure to
lenalidomide, REVLIMID is only available through a restricted
distribution program, the REVLIMID REMS® program.
Information about the REVLIMID REMS
program is available at www.celgeneriskmanagement.com
or by calling the manufacturer's toll-free number
1-888-423-5436.
Hematologic
Toxicity (Neutropenia and Thrombocytopenia)
REVLIMID can cause significant neutropenia and thrombocytopenia.
Eighty percent of patients with del 5q MDS had to have a dose
delay/reduction during the major study. Thirty-four percent of
patients had to have a second dose delay/reduction. Grade 3 or 4
hematologic toxicity was seen in 80% of patients enrolled in the
study. Patients on therapy for del 5q MDS should have their
complete blood counts monitored weekly for the first 8 weeks of
therapy and at least monthly thereafter. Patients may require dose
interruption and/or reduction. Patients may require use of blood
product support and/or growth factors.
Venous and
Arterial Thromboembolism
REVLIMID has demonstrated a significantly increased risk of deep
vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk
of myocardial infarction and stroke in patients with MM who were
treated with REVLIMID and dexamethasone therapy. Monitor for and
advise patients about signs and symptoms of thromboembolism. Advise
patients to seek immediate medical care if they develop symptoms
such as shortness of breath, chest pain, or arm or leg swelling.
Thromboprophylaxis is recommended and the choice of regimen should
be based on an assessment of the patient's underlying risks.
CONTRAINDICATIONS
Pregnancy: REVLIMID can cause fetal harm when
administered to a pregnant female and is contraindicated in females
who are pregnant. If this drug is used during pregnancy or if the
patient becomes pregnant while taking this drug, the patient should
be apprised of the potential risk to the fetus
Severe Hypersensitivity Reactions: REVLIMID is
contraindicated in patients who have demonstrated severe
hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic
epidermal necrolysis) to lenalidomide
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity: See Boxed WARNINGS
- Females of
Reproductive Potential: See Boxed WARNINGS
- Males:
Lenalidomide is present in the semen of patients receiving the
drug. Males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
REVLIMID and for up to 4 weeks after discontinuing REVLIMID, even
if they have undergone a successful vasectomy. Male patients taking
REVLIMID must not donate sperm
- Blood
Donation: Patients must not donate blood during treatment
with REVLIMID and for 4 weeks following discontinuation of the drug
because the blood might be given to a pregnant female patient whose
fetus must not be exposed to REVLIMID
REVLIMID REMS Program: See Boxed
WARNINGS: Prescribers and pharmacies must be certified
with the REVLIMID REMS program by enrolling and complying with the
REMS requirements; pharmacies must only dispense to patients who
are authorized to receive REVLIMID. Patients must sign a
Patient-Physician Agreement Form and comply with REMS requirements;
female patients of reproductive potential who are not pregnant must
comply with the pregnancy testing and contraception requirements
and males must comply with contraception requirements
Hematologic Toxicity: REVLIMID can cause significant
neutropenia and thrombocytopenia. Monitor patients with
neutropenia for signs of infection. Advise patients to observe for
bleeding or bruising, especially with use of concomitant
medications that may increase risk of bleeding. MM: Patients taking
REVLIMID/dex or REVLIMID as maintenance therapy should have their
complete blood counts (CBC) assessed every 7 days for the first 2
cycles, on days 1 and 15 of cycle 3, and every 28 days
thereafter. MDS: Patients on therapy for
del 5q MDS should have their complete blood counts monitored weekly
for the first 8 weeks of therapy and at least monthly thereafter.
Patients may require dose interruption and/or dose reduction.
Please see the Black Box WARNINGS for further
information. MCL: Patients taking REVLIMID
for MCL should have their CBCs monitored weekly for the first cycle
(28 days), every 2 weeks during cycles 2-4, and then monthly
thereafter. Patients may require dose interruption and/or dose
reduction
Venous and Arterial Thromboembolism: See Boxed
WARNINGS: Venous thromboembolic events (DVT and PE) and
arterial thromboses (MI and CVA) are increased in patients treated
with REVLIMID. Patients with known risk factors, including prior
thrombosis, may be at greater risk and actions should be taken to
try to minimize all modifiable factors (e.g., hyperlipidemia,
hypertension, smoking). Thromboprophylaxis is recommended and the
regimen should be based on patient's underlying risks. ESAs and
estrogens may further increase the risk of thrombosis and their use
should be based on a benefit-risk decision
Increased Mortality in Patients with CLL: In a
clinical trial in the first-line treatment of patients with CLL,
single agent REVLIMID therapy increased the risk of death as
compared to single agent chlorambucil. Serious adverse
cardiovascular reactions, including atrial fibrillation, myocardial
infarction, and cardiac failure, occurred more frequently in the
REVLIMID arm. REVLIMID is not indicated and not recommended for use
in CLL outside of controlled clinical trials
Second Primary Malignancies (SPM): In clinical
trials in patients with MM receiving REVLIMID, an increase of
hematologic plus solid tumor SPM, notably AML and MDS, have been
observed. Monitor patients for the development of SPM. Take into
account both the potential benefit of REVLIMID and risk of SPM when
considering treatment
Increased Mortality with Pembrolizumab: In clinical
trials in patients with multiple myeloma, the addition of
pembrolizumab to a thalidomide analogue plus dexamethasone resulted
in increased mortality. Treatment of patients with multiple myeloma
with a PD-1 or PD-L1 blocking antibody in combination with a
thalidomide analogue plus dexamethasone is not recommended outside
of controlled clinical trials
Hepatotoxicity: Hepatic failure, including fatal
cases, has occurred in patients treated with REVLIMID/dex.
Pre-existing viral liver disease, elevated baseline liver enzymes,
and concomitant medications may be risk factors. Monitor liver
enzymes periodically. Stop REVLIMID upon elevation of liver
enzymes. After return to baseline values, treatment at a lower dose
may be considered
Severe Cutaneous Reactions Including Hypersensitivity
Reactions: Angioedema and severe cutaneous reactions
including Stevens-Johnson syndrome (SJS), toxic epidermal
necrolysis (TEN), and drug reaction with eosinophilia and systemic
symptoms (DRESS) have been reported. DRESS may present with a
cutaneous reaction (such as rash, or exfoliative dermatitis),
eosinophilia, fever, and/or lymphadenopathy with systemic
complications such as hepatitis, nephritis, pneumonitis,
myocarditis, and/or pericarditis. These events can be fatal.
Patients with a prior history of Grade 4 rash associated with
thalidomide treatment should not receive REVLIMID. REVLIMID
interruption or discontinuation should be considered for Grade 2-3
skin rash. REVLIMID must be discontinued for angioedema, Grade 4
rash, exfoliative or bullous rash, or if SJS, TEN, or DRESS is
suspected and should not be resumed following discontinuation for
these reactions
Tumor Lysis Syndrome (TLS): Fatal instances of TLS
have been reported during treatment with lenalidomide. The patients
at risk of TLS are those with high tumor burden prior to treatment.
These patients should be monitored closely and appropriate
precautions taken
Tumor Flare Reaction (TFR): TFR has occurred during
investigational use of lenalidomide for CLL and lymphoma.
Monitoring and evaluation for TFR is recommended in patients with
MCL. Tumor flare may mimic the progression of disease (PD). In
patients with Grade 3 or 4 TFR, it is recommended to withhold
treatment with REVLIMID until TFR resolves to ≤Grade 1. REVLIMID
may be continued in patients with Grade 1 and 2 TFR without
interruption or modification, at the physician's discretion
Impaired Stem Cell Mobilization: A decrease in the
number of CD34+ cells collected after treatment ( > 4 cycles)
with REVLIMID has been reported. Consider early referral to
transplant center to optimize timing of the stem cell
collection
Thyroid Disorders: Both hypothyroidism and
hyperthyroidism have been reported. Measure thyroid function before
start of REVLIMID treatment and during therapy
Early Mortality in Patients with MCL: In another MCL
study, there was an increase in early deaths (within 20 weeks),
12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk
factors for early deaths include high tumor burden, MIPI score at
diagnosis, and high WBC at baseline (≥10 x 109/L)
ADVERSE REACTIONS
Multiple Myeloma
- In newly diagnosed: The
most frequently reported Grade 3 or 4 reactions included
neutropenia, anemia, thrombocytopenia, pneumonia, asthenia,
fatigue, back pain, hypokalemia, rash, cataract, lymphopenia,
dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency
of infections occurred in Arm Rd Continuous (75%) compared to Arm
MPT (56%). There were more Grade 3 and 4 and serious adverse
reactions of infection in Arm Rd Continuous than either Arm MPT or
Rd18
- The most common adverse reactions
reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia
(44%), neutropenia (35%), fatigue (33%), back pain (32%), asthenia
(28%), insomnia (28%), rash (26%), decreased appetite (23%), cough
(23%), dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle
spasms (20%), and thrombocytopenia (20%)
- Maintenance Therapy Post
Auto-HSCT: The most frequently reported Grade 3 or 4
reactions in ≥20% (REVLIMID arm) included neutropenia,
thrombocytopenia, and leukopenia. The serious adverse reactions of
lung infection and neutropenia (more than 4.5%) occurred in the
REVLIMID arm
- The most frequently reported adverse
reactions in ≥20% (REVLIMID arm) across both maintenance studies
(Study 1, Study 2) were neutropenia (79%, 61%), thrombocytopenia
(72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper
respiratory tract infection (27%, 11%), bronchitis (5%, 47%),
nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%,
23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%),
asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%,
21%)
- After at least one prior
therapy: The most common adverse reactions reported in
≥20% (REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%),
neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39%
vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia
(28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%),
back pain (26% vs 19%), upper respiratory tract infection (25% vs
16%), dyspnea (24% vs 17%), dizziness (23% vs 17%),
thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs
7%), and weight decreased (20% vs 15%)
Myelodysplastic
Syndromes
- Grade 3 and 4 adverse events reported
in ≥ 5% of patients with del 5q MDS were neutropenia (53%),
thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%),
leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain
(5%)
- Adverse events reported in ≥15% of del
5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia
(58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%),
constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia
(22%), pyrexia (21%), back pain (21%), peripheral edema (20%),
cough (20%), dizziness (20%), headache (20%), muscle cramp (18%),
dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%),
upper respiratory tract infection (15%)
Mantle Cell Lymphoma
- Grade 3 and 4 adverse events reported
in ≥5% of patients treated with REVLIMID in the MCL trial (N=134)
included neutropenia (43%), thrombocytopenia (28%), anemia (11%),
pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%),
dyspnea (6%), and febrile neutropenia (6%)
- Adverse events reported in ≥15% of
patients treated with REVLIMID in the MCL trial included
neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia
(31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%),
rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%),
constipation (16%), and leukopenia (15%)
DRUG INTERACTIONS
Periodic monitoring of digoxin plasma levels is recommended due
to increased Cmax and AUC with concomitant REVLIMID therapy.
Patients taking concomitant therapies such as erythropoietin
stimulating agents or estrogen containing therapies may have an
increased risk of thrombosis. It is not known whether there is an
interaction between dex and warfarin. Close monitoring of PT and
INR is recommended in patients with MM taking concomitant
warfarin
USE IN SPECIFIC POPULATIONS
- PREGNANCY: See Boxed
WARNINGS: If pregnancy does occur during treatment,
immediately discontinue the drug and refer patient to an
obstetrician/gynecologist experienced in reproductive toxicity for
further evaluation and counseling. There is a REVLIMID pregnancy
exposure registry that monitors pregnancy outcomes in females
exposed to REVLIMID during pregnancy as well as female partners of
male patients who are exposed to REVLIMID. This registry is also
used to understand the root cause for the pregnancy. Report any
suspected fetal exposure to REVLIMID to the FDA via the
MedWatch program at 1-800-FDA-1088 and also to Celgene
Corporation at 1-888-423-5436
- LACTATION: There is no
information regarding the presence of lenalidomide in human milk,
the effects of REVLIMID on the breastfed infant, or the effects of
REVLIMID on milk production. Because many drugs are excreted in
human milk and because of the potential for adverse reactions in
breastfed infants from REVLIMID, advise female patients not to
breastfeed during treatment with REVLIMID
- PEDIATRIC USE: Safety and
effectiveness have not been established in pediatric patients
- RENAL IMPAIRMENT: Adjust
the starting dose of REVLIMID based on the creatinine clearance
value and in patients on dialysis
Please see full Prescribing Information,
including Boxed WARNINGS.
About IMNOVID
IMNOVID is a thalidomide analogue indicated, in combination with
dexamethasone, for patients with multiple myeloma who have received
at least two prior therapies including lenalidomide and a
proteasome inhibitor and have demonstrated disease progression on
or within 60 days of completion of the last therapy.
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY and
VENOUS AND ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
- IMNOVID is contraindicated in pregnancy. IMNOVID is a
thalidomide analogue. Thalidomide is a known human teratogen that
causes severe birth defects or embryo-fetal death. In females of
reproductive potential, obtain 2 negative pregnancy tests before
starting IMNOVID treatment.
- Females of reproductive potential must use 2 forms of
contraception or continuously abstain from heterosexual sex during
and for 4 weeks after stopping IMNOVID treatment.
IMNOVID is only available through a
restricted distribution program called POMALYST REMS.Venous
and Arterial Thromboembolism
- Deep venous thrombosis (DVT), pulmonary embolism (PE),
myocardial infarction, and stroke occur in patients with multiple
myeloma treated with IMNOVID. Prophylactic antithrombotic measures
were employed in clinical trials. Thromboprophylaxis is
recommended, and the choice of regimen should be based on
assessment of the patient's underlying risk factors.
CONTRAINDICATIONS
- Pregnancy: IMNOVID can cause
fetal harm and is contraindicated in females who are pregnant. If
IMNOVID is used during pregnancy or if the patient becomes pregnant
while taking this drug, the patient should be apprised of the
potential risk to a fetus.
WARNINGS AND PRECAUTIONS
- Embryo-Fetal
Toxicity & Females of Reproductive Potential: See Boxed
WARNINGS
- Males:
Pomalidomide is present in the semen of patients receiving the
drug. Males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
IMNOVID and for up to 4 weeks after discontinuing IMNOVID, even if
they have undergone a successful vasectomy. Males must not donate
sperm.
- Blood
Donation: Patients must not donate blood during treatment
with IMNOVID and for 1 month following discontinuation of IMNOVID
therapy because the blood might be given to a pregnant female
patient whose fetus must not be exposed to IMNOVID.
- POMALYST
REMS Program: See Boxed WARNINGS
- Prescribers and pharmacies must be
certified with the POMALYST REMS program by
enrolling and complying with the REMS requirements; pharmacies must
only dispense to patients who are authorized to receive IMNOVID.
Patients must sign a Patient-Physician Agreement Form and comply
with REMS requirements; female patients of reproductive potential
who are not pregnant must comply with the pregnancy testing and
contraception requirements and males must comply with contraception
requirements.
- Further information about
the POMALYST REMS program is available
at www.CelgeneRiskManagement.com or by telephone
at 1-888-423-5436.
- Venous and
Arterial Thromboembolism: See Boxed
WARNINGS. Patients with known risk factors,
including prior thrombosis, may be at greater risk, and actions
should be taken to try to minimize all modifiable factors (e.g.,
hyperlipidemia, hypertension, smoking). Thromboprophylaxis is
recommended, and the choice of regimen should be based on
assessment of the patient's underlying risk factors.
- Increased
Mortality with Pembrolizumab: In clinical
trials in patients with multiple myeloma, the addition of
pembrolizumab to a thalidomide analogue plus dexamethasone resulted
in increased mortality. Treatment of patients with multiple myeloma
with a PD-1 or PD-L1 blocking antibody in combination with a
thalidomide analogue plus dexamethasone is not recommended outside
of controlled clinical trials.
- Hematologic
Toxicity: Neutropenia (46%) was the most
frequently reported Grade 3/4 adverse reaction in patients taking
IMNOVID in clinical trials, followed by anemia and
thrombocytopenia. Monitor complete blood counts weekly for the
first 8 weeks and monthly thereafter. Patients may require dose
interruption and/or modification.
- Hepatotoxicity: Hepatic
failure, including fatal cases, has occurred in patients treated
with IMNOVID. Elevated levels of alanine aminotransferase and
bilirubin have also been observed in patients treated with IMNOVID.
Monitor liver function tests monthly. Stop IMNOVID upon elevation
of liver enzymes. After return to baseline values, treatment at a
lower dose may be considered.
- Hypersensitivity
Reactions: Angioedema and severe
dermatologic reactions have been reported. Discontinue IMNOVID for
angioedema, skin exfoliation, bullae, or any other severe
dermatologic reactions, and do not resume therapy.
- Dizziness and
Confusional State: In patients taking
IMNOVID in clinical trials, 14% experienced dizziness (1% Grade 3
or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct
patients to avoid situations where dizziness or confusional state
may be a problem and not to take other medications that may cause
dizziness or confusional state without adequate medical
advice.
- Neuropathy: In patients taking
IMNOVID in clinical trials, 18% experienced neuropathy (2% Grade 3
in one trial) and 12% peripheral neuropathy.
- Second Primary
Malignancies: Cases of acute myelogenous
leukemia have been reported in patients receiving IMNOVID as an
investigational therapy outside of multiple myeloma.
- Tumor Lysis
Syndrome (TLS): TLS may occur in patients
treated with IMNOVID. Patients at risk are those with high tumor
burden prior to treatment. These patients should be monitored
closely and appropriate precautions taken.
ADVERSE REACTIONS
Nearly all patients treated with IMNOVID + low-dose dex
experienced at least one adverse reaction (99%). The most common
adverse reactions (≥15%) included neutropenia (51.3%), fatigue and
asthenia (46.7%), upper respiratory tract infection (31%),
thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%),
diarrhea (22%), constipation (21.7%), back pain (19.7%), cough
(20%), pneumonia (19.3%), bone pain (18%), edema peripheral
(17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and
nausea (15%). Grade 3 or 4 adverse reactions (≥15%) included
neutropenia (48.3%), thrombocytopenia (22%), and pneumonia
(15.7%).
DRUG INTERACTIONS
Avoid concomitant use of IMNOVID with strong inhibitors of
CYP1A2. Consider alternative treatments. If a strong CYP1A2
inhibitor must be used, reduce IMNOVID dose by 50%.
USE IN SPECIFIC POPULATIONS
- Pregnancy: See
Boxed WARNINGS. If pregnancy does occur during
treatment, immediately discontinue the drug and refer patient to an
obstetrician/gynecologist experienced in reproductive toxicity for
further evaluation and counseling. There is an IMNOVID pregnancy
exposure registry that monitors pregnancy outcomes in females
exposed to IMNOVID during pregnancy as well as female partners of
male patients who are exposed to IMNOVID. This registry is also
used to understand the root cause for the pregnancy. Report any
suspected fetal exposure to IMNOVID to the FDA via the
MedWatch program at 1-800-FDA-1088 and also to Celgene
Corporation at 1-888-423-5436.
- Lactation: There is no
information regarding the presence of pomalidomide in human milk,
the effects of IMNOVID on the breastfed infant, or the effects of
IMNOVID on milk production. Pomalidomide was excreted in the milk
of lactating rats. Because many drugs are excreted in human milk
and because of the potential for adverse reactions in breastfed
infants from IMNOVID, advise a nursing woman to discontinue
breastfeeding during treatment with IMNOVID.
- Pediatric
Use: Safety and effectiveness have not been
established in pediatric patients.
- Geriatric
Use: No dosage adjustment is required for
IMNOVID based on age. Patients > 65 years of age were more
likely than patients ≤65 years of age to experience pneumonia.
- Renal
Impairment: Reduce IMNOVID dose by 25% in
patients with severe renal impairment requiring dialysis. Take dose
of IMNOVID following hemodialysis on hemodialysis days.
- Hepatic
Impairment: Reduce IMNOVID dose by 25% in
patients with mild to moderate hepatic impairment and 50% in
patients with severe hepatic impairment.
- Smoking
Tobacco: Advise patients that smoking may
reduce the efficacy of IMNOVID. Cigarette smoking reduces the AUC
of pomalidomide by 32% by CYP1A2 induction.
Please see full Prescribing Information,
including Boxed WARNINGS.
About IDHIFA
IDHIFA (enasidenib) is indicated for the treatment of adult
patients with relapsed or refractory acute myeloid leukemia with an
isocitrate dehydrogenase-2 mutation as detected by an FDA-approved
test.
Important Safety Information
WARNING: DIFFERENTIATION
SYNDROME
Patients treated with IDHIFA have
experienced symptoms of differentiation syndrome, which can be
fatal if not treated. Symptoms may include fever, dyspnea, acute
respiratory distress, pulmonary infiltrates, pleural or pericardial
effusions, rapid weight gain or peripheral edema, lymphadenopathy,
bone pain, and hepatic, renal, or multi-organ dysfunction. If
differentiation syndrome is suspected, initiate corticosteroid
therapy and hemodynamic monitoring until symptom
resolution.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: See Boxed WARNING. In the
clinical trial, 14% of patients treated with IDHIFA experienced
differentiation syndrome. Differentiation syndrome has been
observed with and without concomitant hyperleukocytosis, as early
as 10 days and at up to 5 months after IDHIFA initiation. If
differentiation syndrome is suspected, initiate systemic
corticosteroids and hemodynamic monitoring until improvement. Taper
corticosteroids only after resolution of symptoms. Differentiation
syndrome symptoms may recur with premature discontinuation of
corticosteroids. If severe pulmonary symptoms requiring intubation
or ventilator support and/or renal dysfunction persist for more
than 48 hours after initiation of corticosteroids, interrupt IDHIFA
until signs and symptoms are no longer severe. Hospitalization for
close observation and monitoring of patients with pulmonary and/or
renal manifestation is recommended.
Embryo-Fetal Toxicity: Based on animal embryo-fetal
toxicity studies, IDHIFA can cause embryo-fetal harm when
administered to a pregnant woman. Advise females of reproductive
potential and males with female partners of reproductive potential
to use effective contraception during treatment with IDHIFA and for
at least 1 month after the last dose. Pregnant women, patients
becoming pregnant while receiving IDHIFA, or male patients with
pregnant female partners should be apprised of the potential risk
to the fetus.
ADVERSE REACTIONS
- The most common adverse reactions
(≥20%) included total bilirubin increased (81%), calcium decreased
(74%), nausea (50%), diarrhea (43%), potassium decreased (41%),
vomiting (34%), decreased appetite (34%), and phosphorus decreased
(27%)
- The most frequently reported ≥Grade 3
adverse reactions (≥5%) included total bilirubin increased (15%),
potassium decreased (15%), phosphorus decreased (8%), calcium
decreased (8%), diarrhea (8%), differentiation syndrome (7%),
non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and
nausea (5%)
- Serious adverse reactions were reported
in 77.1% of patients. The most frequent serious adverse reactions
(≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting
(3%), decreased appetite (3%), tumor lysis syndrome (5%), and
differentiation syndrome (8%). Differentiation syndrome events
characterized as serious included pyrexia, renal failure acute,
hypoxia, respiratory failure, and multi-organ failure
LACTATION
Many drugs are excreted in human milk and because of the
potential for adverse reactions in breastfed infants, advise women
not to breastfeed during treatment with IDHIFA and for at least 1
month after the last dose.
Please see full Prescribing Information,
including Boxed WARNING
About Luspatercept
Luspatercept is a modified activin receptor type IIB fusion
protein that acts as a ligand trap for members in the transforming
growth factor-beta superfamily involved in the late stages of
erythropoiesis (red blood cell production). Luspatercept regulates
late-stage erythrocyte (red blood cell) precursor cell
differentiation and maturation. This mechanism of action is
distinct from that of erythropoietin (EPO), which stimulates the
proliferation of early-stage erythrocyte precursor cells. Acceleron
and Celgene are jointly developing luspatercept as part
of a global collaboration. Acceleron and Celgene are
enrolling Phase 3 clinical trials that are designed to evaluate the
safety and efficacy of luspatercept in patients with
myelodysplastic syndromes (the "MEDALIST" study) and in patients
with beta-thalassemia (the "BELIEVE" study). For more information,
please visit www.clinicaltrials.gov.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey,
is an integrated global biopharmaceutical company engaged primarily
in the discovery, development and commercialization of innovative
therapies for the treatment of cancer and inflammatory diseases
through next-generation solutions in protein homeostasis,
immuno-oncology, epigenetics, immunology and neuro-inflammation.
For more information, please visit www.celgene.com.
Follow Celgene on Social
Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements, which
are generally statements that are not historical
facts. Forward-looking statements can be identified by the
words "expects," "anticipates," "believes," "intends," "estimates,"
"plans," "will," "outlook" and similar
expressions. Forward-looking statements are based on
management's current plans, estimates, assumptions and projections,
and speak only as of the date they are made. We undertake no
obligation to update any forward-looking statement in light of new
information or future events, except as otherwise required by law.
Forward-looking statements involve inherent risks and
uncertainties, most of which are difficult to predict and are
generally beyond our control. Actual results or outcomes may
differ materially from those implied by the forward-looking
statements as a result of the impact of a number of factors, many
of which are discussed in more detail in our Annual Report on Form
10-K and our other reports filed with the Securities and
Exchange Commission.
Hyperlinks are provided as a convenience and for informational
purposes only. Celgene bears no responsibility for the
security or content of external websites.
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